1. Field of the Invention
The present invention relates generally to the field of immunology, in particular allergy, and inflammation and compounds effective to modify the operation of such systems and functions. More particularly, it relates to compounds, their preparation and use in the prevention or amelioration of allergic or inflammatory disorders.
2. Brief Description of the Prior Art
Several factors are important in the production of the atopic state of allergic individuals. These factors include the predisposition to produce high levels of IgE against certain antigens and altered sensitivity to the humoral mediators of allergy. Some atopic individuals produce a sustained IgE response when exposed to certain antigens called allergens. The most typical clinical result of antiallergen IgE production is allergy. Allergy is a consequence of the binding of IgE to basophils and mast cells. The combination of allergens with cytophilic IgE leads to cellular degranulation and release of histamine as well as other mediators of the allergic response. See Thaler, et al, Medical Immunology, J. B. Lippincott Co., Philadelphia (1977).
The specific blocking of the histamine (H.sub.1) receptor by certain drugs, the antihistamines, is the basis for their therapeutic efficacy in preventing and treating allergic manifestations of immediate-type hypersensitivity.
Therapy aimed at controlling the symptoms of immediate hypersensitivity reactions with antihistamines is useful but only partially effective. An attractive and advantageous procedure, uniquely applicable to prophylaxis, is to prevent production or release of mediators, such as histamine, by inhibiting responses of sensitized mast cells and basophils to specific antigens. Adrenergic drugs and theophylline, beside their many other other actions, tend to inhibit such allergic responses. This may contribute to the clinical utility. A much more specific inhibition can be achieved, however, with the type of antiallergic drug exemplified by cromolyn sodium. This agent inhibits antigen-induced secretion of histamine from human pulmonary mast cells and from mast cells at certain other sites. Although, the drug is a valuable adjunct in the prophylactic management of certain cases of asthma and certain other atopic states, the usefulness of cromolyn is circumscribed since human basophils, curiously, are not protected. Goodman and Gilman (Eds.), Pharmacological Basis of Therapeutics, 6th Ed, MacMillan Publishing Co., Inc., N.Y. (1980).